EP0950196B1 - Dispositif et procede de localisation nucleaire par calcul de barycentre pondere de detecteurs fonctionnant en parallele, et application aux gamma-cameras - Google Patents

Dispositif et procede de localisation nucleaire par calcul de barycentre pondere de detecteurs fonctionnant en parallele, et application aux gamma-cameras Download PDF

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EP0950196B1
EP0950196B1 EP97952103A EP97952103A EP0950196B1 EP 0950196 B1 EP0950196 B1 EP 0950196B1 EP 97952103 A EP97952103 A EP 97952103A EP 97952103 A EP97952103 A EP 97952103A EP 0950196 B1 EP0950196 B1 EP 0950196B1
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Prior art keywords
event
photodetectors
column
value
gravity
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English (en)
French (fr)
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EP0950196A1 (fr
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Alain Chapuis
Claude Janin
Alain Noca
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Commissariat a lEnergie Atomique et aux Energies Alternatives CEA
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    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01T—MEASUREMENT OF NUCLEAR OR X-RADIATION
    • G01T1/00—Measuring X-radiation, gamma radiation, corpuscular radiation, or cosmic radiation
    • G01T1/16—Measuring radiation intensity
    • G01T1/161—Applications in the field of nuclear medicine, e.g. in vivo counting
    • G01T1/164—Scintigraphy
    • G01T1/1641—Static instruments for imaging the distribution of radioactivity in one or two dimensions using one or several scintillating elements; Radio-isotope cameras
    • G01T1/1642—Static instruments for imaging the distribution of radioactivity in one or two dimensions using one or several scintillating elements; Radio-isotope cameras using a scintillation crystal and position sensing photodetector arrays, e.g. ANGER cameras
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B6/00—Apparatus or devices for radiation diagnosis; Apparatus or devices for radiation diagnosis combined with radiation therapy equipment
    • A61B6/02—Arrangements for diagnosis sequentially in different planes; Stereoscopic radiation diagnosis
    • A61B6/03—Computed tomography [CT]
    • A61B6/037—Emission tomography

Definitions

  • the present invention relates to a device for determination of the position of an inducing event a signal in photodetectors, this position being, for example, spotted with respect to the set photodetectors. Such a position can be spotted by the center of gravity of the event in a landmark linked to photodetectors.
  • the invention applies in particular to the determining the position of an event from signals provided by photomultipliers equipping a gamma camera, the position being located relative to to the photomultipliers themselves.
  • gamma camera a camera sensitive to gamma radiation ( ⁇ ).
  • ⁇ gamma radiation
  • gamma cameras allow visualize the distribution, in an organ, of molecules marked by a radioactive isotope injected to the patient.
  • Figure 1 shows a detection head 10 a gamma camera arranged in front of an organ 12 containing molecules labeled with a radioactive isotope.
  • the detection head 10 comprises a collimator 20, a scintillator crystal 22, a light guide 24 and a plurality of photomultiplier tubes 26 juxtaposed so as to cover one side of the guide of 24.
  • the scintillator is, for example, a NaI crystal (Tl).
  • the purpose of the collimator 20 is to select from all gamma radiation 30 emitted by the organ 12 those who reach the head of sensing substantially under normal incidence.
  • the selective nature of the collimator makes it possible to increase resolution and sharpness of the image produced.
  • the increase in the resolution is done at detriment of sensitivity. For example, for about 10,000 ⁇ photons emitted by the organ 12, a single photon is actually detected.
  • Photomultipliers 26 are designed to send a proportional electrical pulse number of light photons received from the scintillator for each event.
  • the photomultipliers 26 are not directly contiguous to the scintillator crystal 22 but are separated from this last by the light guide 24.
  • Photomultipliers emit a signal whose amplitude is proportional to the quantity total light produced in the scintillator by a gamma radiation, that is to say, proportional to its energy.
  • the individual signal of each photomultiplier also depends on the distance that the separates from the interaction point 30 of gamma radiation with the scintillator material. Indeed, every photomultiplier delivers a current pulse proportional to the luminous flux he has received.
  • small graphs A, B, C show that photomultipliers 26a, 26b and 26c located at different distances from an interaction point 30 deliver signals with amplitudes different.
  • the position of the interaction point 30 of a gamma photon is calculated in the gamma-camera from signals from all of the photomultipliers by weighting barycentric contributions of each photomultiplier.
  • Figure 2A shows the electrical wiring of a detection head 10 of a gamma camera, which connects this camera to a unit forming an image.
  • the detection head has a plurality of photomultipliers 26.
  • each photomultiplier 26 of the detection head is associated with four resistors denoted RX - , RX + , RY - and RY + .
  • the values of these resistors are specific to each photomultiplier and depend on the position of the photomultiplier in the detection head 10.
  • each photomultiplier is connected to the output 50 of said photomultiplier, shown in FIG. 2B with a current generator symbol. They are, on the other hand, respectively connected to common collecting lines denoted LX - , LX + , LY - , LY + , in FIG. 2A.
  • the lines LX - , LX + , LY - and LY + are in turn connected respectively to analog integrators 52X - , 52X + , 52Y - , 52Y + , and via these to analog / digital converters.
  • 54X - , 54X + , 54Y - , 54Y + The output of the converters 54X - , 54X + , 54Y - , 54Y + is directed to a digital operator 56.
  • the lines LX - , LX + , LY - , LY + are also connected to a common channel, called energy path. This channel also comprises an integrator 57 and an analog / digital converter 58 and its output is also directed towards the operator 56.
  • the calculation of the position of the interaction is tainted with uncertainty about fluctuations Poisson statistics of the number of light photons and the number of photoelectrons produced for each event, that is to say for each gamma photon detected.
  • the standard deviation of fluctuation is all the lower than the number of photons or photoelectron is high. Because of this phenomenon, he should collect the light most carefully possible.
  • the intrinsic spatial resolution of the camera is characterized by the width at half height of the distribution of calculated positions for the same collimated point source placed on the crystal scintillator.
  • the resolution is generally of the order of 3 to 4 mm.
  • the energy of a detected gamma photon is calculated by summing the contributions of all photomultipliers having received light. She is also tainted by a statistical fluctuation.
  • the energy resolution of the camera is characterized by the ratio of the halfway width of the distribution of calculated energies to the average value distribution, for the same source.
  • the energy resolution is usually the order of 9 to 11% for gamma rays of an energy 140 keV.
  • a gamma-camera type Anger has the advantage of being able to calculate time real the center of gravity of the photomultiplier signals with very simple means.
  • the system described previously has a limited number of components.
  • the resistors used to inject the signal from photomultipliers in the collector lines are very inexpensive.
  • U.S. Patent No. 5,576,547 proposes a method to correct the calculation of the total energy received by the detectors and deduce a corrected position of the event.
  • Correction tables are established in building for known positions of events histograms of the energy captured by the different detectors.
  • a camera such as the ANGER camera presents however also a major disadvantage which is a rate counting reduced.
  • Count rate means the number of events, that is, interactions between a ⁇ photon and the scintillator, that the camera is able to process per unit of time.
  • the device described in this application includes means for digitizing the signal provided by each detector and the energy of each photodetector is calculated with a correction for take into account the energy brought by events occurring while the current event is still In progress.
  • the collimator stops a very large number of gamma rays and only a small number events are actually detected.
  • Gamma cameras are however used also in two other imaging techniques medical system where the limitation of the count rate is a crippling constraint.
  • the mitigation correction technique by transmission is to take into account, when formation of a medical image, of the own attenuation tissue of the patient surrounding the examined organ. For know this attenuation, we measure the transmission gamma radiation to a gamma camera through the body of the patient. For this purpose we take place to the patient between a very active external source and the detection head of the gamma camera. So, during the measurement of transmitted radiation, a high number events take place in the scintillator crystal. The high number of events per unit of time increases also the probability of having multiple events substantially simultaneous. Anger-type camera classic then turns out to be inappropriate.
  • the PET technique consists of injecting the patient with an element such as F 18 capable of emitting positrons.
  • the annihilation of a positron and an electron releases two ⁇ photons emitted in opposite directions and having an energy of 511 keV.
  • This physical phenomenon is used in the PET imaging technique.
  • a gamma camera is used with at least two detection heads arranged on either side of the patient.
  • the detection heads used are not equipped with a collimator. Indeed, an electronic processing of the information, said treatment of coincidence, makes it possible to select among the events those which coincide temporally, and to calculate thus the trajectory of the gamma photons.
  • the detection heads are therefore subject to high gamma radiation flux.
  • Gamma cameras Anger classics have a count rate generally too limited for such an application.
  • an Anger type gamma camera can function normally with a detection of 1.10 5 events per second, while in PET imaging it takes at least 1.10 6 events per second for normal operation.
  • Such a method makes it possible to process digitized data, and makes it possible to produce a position signal P 0 , or, more precisely, a pair of barycentric coordinates (X 0 , Y 0 ) of the event with respect to all the N photodetectors.
  • the high count rate is reached without restrict the number of photodetectors read. This is due to the parallelism used, and the strong "pipelinage", that is to say, the succession of simple operations.
  • the method according to the invention makes it possible to accelerate the calculation of the center of gravity digitized contributions from photodetectors, parallelizing this calculation.
  • the invention also relates to a device for implementing the method described above.
  • the invention will be described in a manner detailed for photomultipliers of a gamma camera. However, this description also applies to any photodetectors, which do not necessarily part of a gamma camera.
  • FIG. 3 represents a set of photomultipliers 60, 60-1, 60-2, ... constituting a gamma-camera head.
  • Each photomultiplier is identified by its position (i, j) in all the photomultipliers. More precisely, XC i, j and YC i denote the coordinates, along two axes X, Y, of the center of the photomultiplier i, j.
  • each of the photomultipliers is digitized and processed individually (integration, corrections, etc.).
  • Each photomultiplier has a level of storage register that can memorize the contribution of each photomultiplier during the detection of an event.
  • the network of photomultipliers is organized in rows and columns, and all the outputs of the photomultiplier storage registers of a same column are connected on a bus 62 (bus column).
  • Column buses can be collected in one 64 series bus.
  • Means 66 make it possible to select each column independently of the others. These means 66 are for example, controlled by a sequencer 68 ( Figure 4).
  • a coarse position of the event is first determined, for example by a method to be described later, in connection with the figure 15.
  • the reading time of the registers of storage to handle an event is a passage obliged which directly influences the count rate of the machine (number of events handled by second).
  • Figure 4 illustrates more precisely a device for implementing the invention.
  • a read sequencer 68 makes it possible to read the contents of the storage register of each photomultiplier.
  • N i, j be the contents of the storage register of the column photomultiplier i and line j.
  • N i, j is actually, for example, a digital integral of the signal delivered by the photomultiplier i, j in response to an event.
  • Means 70 make it possible to determine a presumed or gross position of the event. These means will be described further in a more detail ( Figure 15).
  • the command sequencer 68 the addressing of the columns by a multiplexer 74.
  • the contribution of each column to the total energy, to the X component of the center of gravity (XC) and the component in Y of the center of gravity (YC) is transferred to a system of calculation 76, either by addressing the columns via the multiplexer, either directly by the sequencer of calculation 68.
  • N 1 photomultipliers N 1 ⁇ N
  • the sequencer can be realized in form EPROM. At each presumed position corresponds a page memory in which the commands and values needed for calculation. This page is read online per line using a counter 72 which activates the low addresses of the EPROMs.
  • FIG. 5 represents means 80 associated with each column and subsequently called operator column.
  • each column bus output is connected to the input of a column operator 80.
  • Each column 80 operator completes three operations, preferably in parallel.
  • a first operation consists in calculating the contribution of the column to the energy. For example, after being initialized at the beginning of the sequence, an accumulator 82 sums the values N i, j of the 6 photomultipliers of the column and stores the result in a register 84 (CSsch). The outputs of the 6 registers (RSEcol1 to RSEcol6) are grouped on a common BECOL bus.
  • a second operation is to calculate the contribution of the column to the centroid in X.
  • a multiplier-accumulator 86 performs the sum of the contributions to the center of gravity in X of the 6 photomultipliers of the column, and stores the result in a register 88 (RSXcol).
  • the outputs of 6 registers (RSXcol1 to RSXco16) are grouped on one BXCOL common bus.
  • a third operation is to calculate the contribution of the column to the centroid in Y.
  • a second multiplier-accumulator 90 performs the sum of contributions to the center of gravity Y of the 6 photomultipliers of the column, and stores the result in a register 92 (RSYcol).
  • the outputs of 6 registers (RSYcol1 to RSYco16) are grouped on one BYCOL common bus.
  • the values N i, j of the photomultipliers and the coordinates XC i, j and YC i, j are stored in a system 94 of the FIFO type so that they can be used subsequently.
  • a battery 96 after being initialized at the beginning of the sequence, powered by the BECOL bus, calculates the sum of the six RSEcol1 registers1 to RSEcol6 and stores the result in a register 98 (ENERGY).
  • the content of this register represents the sum of contributions to the energy of 36 photomultipliers surrounding the presumed position, so the energy of the event.
  • a second accumulator 100 powered by the BXCOL bus, calculates the sum of the six registers RSXcol1 to RSXcol6, and stores the result in a register 102 (RXN). The contents of this register represent
  • a third accumulator 104 powered by the BYCOL bus, performs the sum of the six RSYcol1 registers RSYcol6, and stores the result in a register 106 (RYN) - The content of this register represents
  • the RSEcol, RSXcol and RSYcol registers are then released so that they can be used by column operators, and accumulators are well again available to process a new event.
  • X 0 RXN / ENERGY
  • Y 0 RYN / ENERGY and this in less than 6 read times to be able to release the storage registers 98, 102, 106.
  • the integrated pipelined integrated dividers (of the RAYTHEON 3211 type, for example) are capable of largely assuming these performances and even make it possible to use only one housing, performing the two divisions successively.
  • This function K is determined so empirical and adapted to each type of photomultiplier and at every collection geometry light.
  • a first example of function K (d) is given in FIG. 7A.
  • This first example corresponds to 75 mm square photomultipliers. Values of K for particular values of d (with a pitch of 5 mm) are given in Table I below.
  • a second example of function K (d) is given in FIG. 7B.
  • This second example corresponds to hexagonal photomultipliers of 60 mm.
  • Values of K for particular values of d (with a pitch of 5 mm) are given in Table II below.
  • the weighted barycentre is calculated in the same way as the gross centroid, after replacing N i, j by N ' i, j .
  • the calculation of the gross centroid is followed by a weighting operation with the function K, called the weighting function.
  • this task is performed by 6 operators, each of them being able to process 6 contributions in 6 read times.
  • N ' i, j is easily achievable because each computation step is simple enough to be performed during the duration of a reading step (typically 100 nsec).
  • the weighted center of gravity output gives the new coordinates X 1 , Y 1 of the position of the event.
  • care is taken to advance the value of the energy parallel to the calculations; at the final output, in the same register 152, the energy and the coordinates of the event are obtained.
  • the calculation of the weighted center of gravity allows to improve the accuracy of the position.
  • An embodiment of calculation of the weighted barycentre and the filtered energy is given in FIG.
  • Steps 156-1, 156-2, 156-3, 156-4 are identical to steps 116-1, 116-21, 116-3, 116-4.
  • d 2 is compared with a value D 2 , where D is the distance, from the point of interaction P 0 , beyond which it is estimated that the signal / noise of the contribution of a photomultiplier is too low.
  • step 156-6 in a register 143, in addition to the values N ' i, j , XC i, j and YC i, j , is stored the value N i, j * PD (actually 0 when d 2 > D 2 and N i, j when d 2 ⁇ D 2 ).
  • FIG. 12 represents a column operator 180. It receives, in addition to the values N i, j and N i, j * PD of the photomultipliers of the column, the coordinates XC i, j and YC i, j of the photomultiplier centers. corresponding, provided by the computing subsystem 168.
  • Each column operator 180 completes 4 operations, preferably in parallel.
  • a first operation consists in calculating the contribution of the column to the energy. For example, after having been initialized at the beginning of the sequence, an accumulator 191 makes the sum of the values N i, j * PD of the 6 photomultipliers of the column and stores the result in a register 193 (RSENcol). The outputs of the 6 registers (RSENcol1 to RSENcol6) are grouped on a common BENCOL bus.
  • a second operation consists of calculating, for the corresponding column, the sum ⁇ N ' i, j .
  • an accumulator 182 is summed ⁇ N ' i, j for the 6 photomultipliers of the column, and stores the result in a register 184.
  • a third operation is to calculate the contribution of the column to the centroid in X.
  • a multiplier-accumulator 186 performs the sum of the contributions to the center of gravity in X of the 6 photomultipliers of the column, and stores the result in a register 188 (RSXcol).
  • the outputs of 6 registers (RSXcol1 to RSXco16) are grouped on one BXCOL common bus.
  • a fourth operation is to calculate the contribution of the column to the centroid in Y.
  • a second multiplier-accumulator 190 makes the sum of contributions to the center of gravity Y of the 6 photomultipliers of the column, and stores the result in a register 192 (RSYcol).
  • the outputs of 6 registers (RSYcol1 to RSYcol6) are grouped on one BYCOL common bus.
  • An accumulator 195 having been initialized at the beginning of the sequence, powered by the BENCOL bus, calculates the sum of the six registers RSENcol1 to RSENcol6 and stores the result in a register 197 (ENERGY).
  • the contents of this register represent the sum of the corrected contributions N i, j * PD at the energy of the 36 photomultipliers surrounding the presumed position, therefore the energy of the event.
  • a second accumulator 196 after having been initialized at the beginning of the sequence, powered by the bus BECOL calculates the sum of the 6 RSEcol1 registers to RSEcol6 and stores the result in a register 198.
  • a third accumulator 200 powered by the BXCOL bus, calculates the sum of the six registers RSXcol1 to RSXcol6, and stores the result in a register 202 (RXN). The contents of this register represent
  • a fourth accumulator 204 powered by the BYCOL bus, sums the six registers RSYcol1 to RSYco16, and stores the result in a register 206 (RYN). The contents of this register represent
  • the RSEcol, RSXcol and RSYcol registers are then released so that they can be used by column operators, and accumulators are well again available to process a new event.
  • RX 1 and RY 1 of the interaction point of the event are calculated by performing two divisions using a divider 208:
  • RX 1 RXN / ⁇ N ' i, j
  • RY 1 RYN / ⁇ N ' i, j and this in less than 6 read times to be able to release the storage registers 198, 202, 206.
  • the integrated pipelined integrated dividers (of the RAYTHEON 3211 type, for example) are capable of largely assuming these performances and even make it possible to use only one housing, performing the two divisions successively.
  • Registers 210 and 212 therefore contain the corrected coordinate values as well as the value corrected energy of the event.
  • the system according to the invention requires electronics important, the fact remains that it is very competitive with systems employing programmable calculating means (microprocessors or DSP). Especially since in certain configurations he can see his realization significantly simplified. This is the case, for example, with a gamma camera head composed of square photomultipliers assumes that the photomultiplier centers are on a regular and square mesh. We can then use a notion of pitch (distance in X and in Y between the centers of the two contiguous photomultipliers) that simplifies most operators.
  • Figure 14 shows the part of the device associated with a single photomultiplier 60.
  • the photomultiplier 60 connected to a converter current-voltage 262.
  • a signal on the output 264 of the current-voltage converter 262 by example of the type of the one shown in the figure 15A.
  • the graph of FIG. 15A indicates, on the ordinate, the amplitude of the signal corresponding to the pulse and, on the abscissa, the time.
  • the amplitude of the signal and the time are indicated in arbitrary scale.
  • t 0 denotes the start time of the pulse provided by the photodetector and t 1 the moment when the pulse returns to almost zero after having passed through a maximum.
  • the duration corresponding to the interval t 1 -t 0 is of the order of one microsecond, in the case of a photomultiplier of a gamma-camera coupled to an NaI crystal (Tl).
  • the analog signal present on the terminal of output 264 is directed to a converter analog-digital 266.
  • the latter samples each pulse of the signal into a number of samples n, as illustrated in FIG. 15B. Two consecutive samples are separated by a step, or clock interval p (the clock running at 1 / p Hz).
  • the analog-digital converter 266 is, preferably, a fast converter, of type "Flash" capable of operating at a frequency of the order of 10 to 20 megahertz.
  • the digital signal from the converter analog-digital 266 directed to an adder number 268.
  • This summoner makes a sum of the samples sent to it by the analog-digital converter 266.
  • the sum slippery is performed on a given number of samples. This predetermined number is equal, by example, at 10.
  • this sliding sum, or digital integral of the signal delivered in response to an event corresponds to the magnitude N i, j already introduced above.
  • the result of the summation carried out with the means 268 is stored in a register 271.
  • the storage function can be composed of several registers to allow memorize several events temporally very relatives.
  • the value of the sliding sum is directed to means of comparison 270.
  • the value of the sliding sum is compared with a threshold value predetermined set at an input 272 of the comparator 270.
  • This comparator transmits on an output 274 a signal binary, representative of the result of the comparison (for example, 0 if the value of the sliding sum is below the set reference value and 1 if the value of the sliding sum is greater than the value reference).
  • This window is positioned taking as reference the time of passage of the coded signal by a maximum.
  • This detection is performed by the means 288 by comparing the current value of the output of the encoder to the previous value. When the current value is lower than the previous value, the comparator 288 emits a pulse. This pulse is sent to a shift register 290 whose delay n 1 is set to generate a time window centered on the maximum of the sliding sum.
  • An AND gate 292 whose inputs are the signal obtained at the output of the comparator 270, and the output signal from the shift register 290, allows to obtain, on its output 294, a passing signal threshold at the desired moment in relation to the passage through the maximum of the digital signal.
  • Figure 16 shows a device, compliant to the invention, for the processing of signals from several photodetectors 60, 60-1, 60-2.
  • references identical to those of the figure 14 designate similar elements or correspondents.
  • the reference 302 designates globally all the analog signals taken from the other current-voltage converters 262-1, 262-2, .... All of these signals fit into a summator analog 298 which delivers a signal S, sum of all the analog signals provided by a number photodetectors, for example by all photodetectors.
  • a device 304 makes it possible to deliver a pulse I during the passage of the signal S by its maximum.
  • This device 304 comprises, for example, a differentiator (capacitance, amplifier and resistors between the input and the output of the amplifier); the output of this differentiator feeds a comparator which makes it possible to detect the passage to 0 of the output of the differentiator.
  • Pulse I feeds the input of a shift register 306 whose pitch p is set by the clock H.
  • the output 307 of this register is called memorization pulse and allows, in particular, to trigger the memory register 271 corresponding to the photodetector 60. It triggers also each memory register associated with each photodetector.
  • the delay of the shift register 306 is set so that the rising edge of the memory signal 307 is synchronous with the moment where we have to memorize the sums in the registers 271.
  • the set of photodetectors 60, 60-1, 60-2, ... is distributed for example in a network two-dimensional.
  • the type 422 signals are the addresses of a PROM 276 who. is programmed to provide the coordinate (280) of the presumed position to the columns.
  • type 432 signals are the addresses of a second PROM 277 which is programmed from to provide the coordinate (281) of the position presumed in relation to the lines.
  • the presumed position, represented by the pair of values (280, 281), is stored in a register 322, at the same time as memorize the contribution of all photodetectors in their respective registers (271). This memorization is triggered by the signal 307 generated by register 306.

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EP97952103A 1996-12-31 1997-12-18 Dispositif et procede de localisation nucleaire par calcul de barycentre pondere de detecteurs fonctionnant en parallele, et application aux gamma-cameras Expired - Lifetime EP0950196B1 (fr)

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FR9616294A FR2757955B1 (fr) 1996-12-31 1996-12-31 Dispositif et procede de localisation nucleaire par calcul de barycentre parallelise, et application aux gamma-cameras
FR9616294 1996-12-31
PCT/FR1997/002349 WO1998029762A1 (fr) 1996-12-31 1997-12-18 Dispositif et procede de localisation nucleaire par calcul de barycentre pondere de detecteurs fonctionnant en parallele, et application aux gamma-cameras

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EP0950196B1 true EP0950196B1 (fr) 2003-03-19

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US6603125B1 (en) * 2000-06-02 2003-08-05 Koninklijke Philips Electronics, N.V. Event localization and fall-off correction by distance-dependent weighting
FR2810172B1 (fr) * 2000-06-13 2004-10-15 Commissariat Energie Atomique Procede de conversion d'un signal analogique en signal numerique et detecteur de rayonnements electromagnetiques utilisant ce procede
JP4696172B2 (ja) * 2009-06-15 2011-06-08 古河機械金属株式会社 信号光検出装置及び信号光検出方法
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JP2001507450A (ja) 2001-06-05
FR2757955B1 (fr) 1999-01-29
DE69720046D1 (de) 2003-04-24
DE69720046T2 (de) 2003-12-11
EP0950196A1 (fr) 1999-10-20
FR2757955A1 (fr) 1998-07-03
US6333503B1 (en) 2001-12-25
WO1998029762A1 (fr) 1998-07-09

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